Orchestrating Evidence Needs: Overcoming Regulatory and National HTA Hurdles Without Delays

Optimising evidence generation in trial design, while navigating regulatory and local payer requirements across markets, remains a key challenge for pharmaceutical manufacturers. Indeed, failure to anticipate evidence needs early in the drug development process can often lead to immature data packages and suboptimal HTA outcomes, that ultimately result in delays in access and unrealised price potential. These challenges are more pertinent now than ever, as healthcare systems continue to grapple with rising treatment costs, and payers step up reimbursement scrutiny as high-cost innovative therapies replace older, lower-cost off-patent standard of care. 

Recent examples include lebrikizumab and elranatamab, neither of which met the strict HTA evidence criteria in France and Germany, due to a lack of relevant comparative data and significant uncertainty around patient-relevant benefits.^1,2 These examples are just part of a bigger trend indicating that positive HTA outcomes have become more elusive in recent years³ – according to data released by the Transparency Commission showing that the percentage of new drugs receiving an ASMR rating I-III (which allow the possibility of price premiums) decreased by 12% and the percentage of drugs receiving an ASMR rating of V (no additional benefit) increased by 13% between 2021 and 2024.³

Data collected by EFPIA’s European Access Hurdles portal showed that the most likely reason (38%) that manufacturers did not file for pricing and reimbursement in the EU4+UK was due to the evidence package being unlikely to meet country requirements⁸, illustrating the need to align evidence strategy with the needs of payers early on.

It is important to also note that with a rapidly evolving HTA environment in Europe, additional opportunities to optimise evidence strategy are emerging. For instance, at national level, initiatives such as the introduction of alternative value metrics such as NHS productivity in the UK and the Netherlands, which offer opportunities for expanded value demonstration beyond traditional clinical endpoints. ^4-7

Benefits of early payer engagement

Early payer engagement is a crucial component of a successful market access strategy, as it can help significantly reduce risks by ensuring that the evidence generated answers the right clinical, economic and societal questions. Incorporating early scientific advice into trial design can help manufacturers build a strong value proposition and obtain much-needed KOL support. Furthermore, a well-informed evidence package can reduce HTA hurdles by ensuring submissions are relevant and unambiguous, minimising the need for prolonged clarification or additional data requests. Carefully considering payer requirements and priorities early on is key to reducing payer uncertainty and lowering the risk of population restrictions, conditional reimbursement, and potential access delays. Beyond HTA, early payer engagement also serves as an important strategic imperative for making go-or-no-go pipeline investment decisions. It helps manufacturers to avoid HTA hurdles by prioritising the development of therapies that can address patient-relevant unmet needs, improve healthcare efficiency and demonstrate value to society.

What key strategic areas can early payer engagement inform?

Population

• Define trial populations that reflect real-world practice and payer expectations, not just narrow inclusion/exclusion criteria and recruiting from certain geographic regions
• Pre-plan subgroup analyses for priority patient groups to demonstrate differential benefit.

Intervention

• Clearly position the therapy within the treatment pathway (e.g., line of therapy, add-on vs monotherapy).
• Ensure dosing, mode of administration, and treatment duration are transparent and implementable in clinical practice.

Comparator

• Select comparators that reflect the standard of care in priority markets; regulators may accept placebo-controlled trials, but most European HTA agencies expect active comparators.
• Confirm comparator choices early with HTA bodies to prevent gaps that lead to indirect treatment comparisons (ITCs) or additional studies.
• Consider differences across markets (e.g., first-line vs second-line treatments) and build in flexibility.

Outcomes

• Incorporate payer-relevant endpoints beyond efficacy and safety, such as quality of life, durability of effect, healthcare resource use, and productivity gains.
• Include validated surrogate endpoints where long-term outcomes are not yet mature, ensuring they are clearly linked to patient benefit.
• Explore novel metrics (equity, environmental impact, system efficiency) where these are increasingly recognised in HTA assessments.

Further opportunities for enhanced value demonstration by leveraging evolving value frameworks

Beyond traditional endpoints and trial design, manufacturers can further strengthen their value proposition by incorporating novel metrics into their evidence generation strategies that align with evolving payer and societal priorities. Recently, there has been a trend among European HTA agencies to broaden value metrics and increase the weighting towards alternative metrics for reimbursement outcomes and market access. Specifically, in the UK, NHS productivity and health inequality metrics have aided the reimbursement of several drugs such as Opdivo and Casgevy. In the Netherlands, environmental considerations such as climate impact, measured by CO2 equivalents, carbon budget, and greenhouse gas emissions, and NHS productivity, measured by labour utilisation, have also been recently included in assessments.^7,9 Leveraging both traditional and newer value metrics offers significant opportunities for differentiation and further maximising value demonstration in areas that payers previously overlooked.

Designing studies, planning for HTA, or needing strategy validation mid-process? Remap partners with companies to provide evidence generation, HTA strategy, and reimbursement expertise. Get in touch with us.

References

1. https://www.has-sante.fr/jcms/p_3524686/fr/ebglyss-lebrikizumab; https://www.aerztezeitung.de/Politik/Fehlende-Daten-G-BA-kann-keinen-Zusatznutzen-feststellen-450213.html
2. .https://www.has-sante.fr/jcms/p_3517411/fr/elrexfio-elranatamab-myelome-multiple; https://www.dgho.de/publikationen/stellungnahmen/fruehe-nutzenbewertung/elranatamab/elranatamab-dgho-dsmm-gmmg-20240505.pdf
3. https://www.has-sante.fr/upload/docs/application/pdf/2025-04/rapport_dactivite_2024_de_la_ct.pdf
4. https://assets.publishing.service.gov.uk/media/6888a0b1a11f859994409147/fit-for-the-future-10-year-health-plan-for-england.pdf
5. https://diariofarma.com/2025/04/09/que-cambia-del-borrador-filtrado-al-texto-oficial-de-la-nueva-ley-de-los-medicamentos
6. https://www.nice.org.uk/news/blogs/health-inequalities-an-update-to-nice-s-methods-for-health-technology-evaluation
7. https://www.zorginstituutnederland.nl/documenten/2025/05/21/advies-van-de-commissie-arbeidsinzet-en-duurzaamheid
8. https://www.efpia.eu/media/lrbdpuoz/cra-efpia-european-access-hurdles-portal-2025.pdf
9. https://www.england.nhs.uk/2025/04/nhs-rolls-out-5-minute-super-jab-for-15-cancers/